Indirect Treatment Comparison of Inotuzumab Ozogamicin Versus Blinatumomab for Relapsed or Refractory Acute Lymphoblastic Leukemia

Adv Ther. 2019 Aug;36(8):2147-2160. doi: 10.1007/s12325-019-00991-w. Epub 2019 May 28.

Abstract

Introduction: No head-to-head studies have compared inotuzumab ozogamicin (InO) and blinatumomab (Blina) for the treatment of adults with relapsed or refractory B cell precursor acute lymphoblastic leukemia (ALL). Indirect treatment comparisons (ITCs), namely network meta-analysis (NMA), anchored matching-adjusted indirect comparison (MAIC), and simulated treatment comparison (STC), were conducted to compare the relative efficacy of these therapies.

Methods: Patient-level data from a study that evaluated InO with standard of care (SoC) chemotherapy (INO-VATE-ALL) and published data from a study that evaluated Blina with SoC chemotherapy (TOWER) were used in the analyses. Endpoints evaluated included remission rate defined as complete remission or complete remission with incomplete hematologic recovery (CR/CRi), hematopoietic stem cell transplantation (HSCT), overall survival (OS), and event-free survival (EFS). For each outcome, treatment-effect modifiers were adjusted for in the anchored MAIC and STC analyses.

Results: Analyses showed statistically significant higher rates of remission and HSCT with InO compared to Blina irrespective of the ITC method used or measure of the effect (i.e., odds ratio [OR] or rate difference). The treatment effects derived from the MAIC and STC analyses were consistent and stronger than those estimated from the NMA. A trend favoring InO was detected for EFS. The ITC results for OS suggest no difference between InO and Blina.

Conclusion: Results from these ITCs indicated a statistically significant advantage for InO over Blina for rates of remission and HSCT in adults with relapsed or refractory B cell precursor ALL. It was not possible to fully adjust for all treatment-effect modifiers, and the similarity in chemotherapy regimens used in the SoC comparator arms of the INO-VATE-ALL and TOWER studies is worthy of further exploration. Both studies, however, used chemotherapy regimens that have a low response rate; therefore, no significant differences in efficacy outcomes are expected between SoC arms.

Funding: Pfizer Inc, New York, NY. Plain language summary available for this article.

Keywords: Blinatumomab; Indirect treatment comparison; Inotuzumab ozogamicin; Matching-adjusted indirect comparison; Relapsed or refractory acute lymphoblastic leukemia; Simulated treatment comparison.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antibodies, Bispecific / therapeutic use*
  • Antineoplastic Agents / therapeutic use*
  • Antineoplastic Agents, Immunological / therapeutic use*
  • Disease-Free Survival
  • Female
  • Humans
  • Inotuzumab Ozogamicin / therapeutic use*
  • Male
  • Middle Aged
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / drug therapy*
  • Remission Induction*
  • Standard of Care
  • Young Adult

Substances

  • Antibodies, Bispecific
  • Antineoplastic Agents
  • Antineoplastic Agents, Immunological
  • blinatumomab
  • Inotuzumab Ozogamicin

Associated data

  • figshare/10.6084/m9.figshare.8109149